Identification of amino acid residues that control functional behavior in GluR5 and GluR6 kainate receptors

Neuron. 1997 Oct;19(4):913-26. doi: 10.1016/s0896-6273(00)80972-1.


GluR5 and GluR6 kainate receptors differ in their responses to a variety of agonists, despite their relatively high primary sequence homology. We carried out a structure-function study to identify amino acids underlying these divergent responses. Patch clamp analysis of chimeric GluR5-GluR6 receptors indicated that several functionally dominant sites were localized to the C-terminal side of M1. All nonconserved amino acids in the region between M3 and M4 of GluR6 were then individually mutated to their GluR5 counterparts. We found that a single amino acid (N721 in GluR6) controls both AMPA sensitivity and domoate deactivation rates. Additionally, mutation of A689 in GluR6 slowed kainate desensitization. These functional effects were accompanied by alterations in binding affinities. These results support a critical role for these residues in receptor binding and gating activity.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution
  • Binding Sites
  • Cell Line
  • Cell Membrane / physiology
  • Conserved Sequence
  • Evoked Potentials / drug effects
  • Humans
  • Ion Channel Gating
  • Kainic Acid / pharmacology*
  • Models, Structural
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Patch-Clamp Techniques
  • Protein Structure, Secondary*
  • Receptors, Kainic Acid / biosynthesis
  • Receptors, Kainic Acid / chemistry*
  • Receptors, Kainic Acid / physiology*
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • Sequence Alignment
  • Transfection


  • Gluk1 kainate receptor
  • Gluk2 kainate receptor
  • Receptors, Kainic Acid
  • Recombinant Fusion Proteins
  • Kainic Acid